Intermittent Theta-Burst Stimulation (iTBS) Modulates Abnormal Brain Activity During Emotional Arousal in Adolescent Depression: A Pilot Study.

The rising incidence of adolescent depression in China causes significant impairments, necessitating rapid treatments such as accelerated Intermittent theta-burst stimulation (iTBS). However, responses to treatment vary. We used naturalistic functional magnetic resonance imaging (N-fMRI) to investigate the impact of depression on the neural processing of emotional arousal. The objectives of this study were: 1) to identify brain regions associated with treatment response, and 2) to correlate these neural signatures with clinical outcomes following accelerated iTBS.Fifty-eight adolescents with depression and twenty-nine healthy controls underwent fMRI while viewing emotion-evoking videos. Forty-three patients completed accelerated iTBS treatment, with pre- and post-treatment fMRI scans. Statistical analysis of the MRI data was performed in SPM12, employing cluster-based family-wise error correction at a significance threshold of p < 0.05.Whole-brain analysis revealed that adolescents with depression exhibited significantly reduced emotion-arousal activation in the left superior frontal gyrus (L-SFG) and left middle frontal gyrus (L-MFG) compared to healthy controls during high-to-medium emotional arousal. Hamilton Depression Scale scores significantly decreased after iTBS treatment. L-MFG showed a marginally significant increase in emotion-arousal activation after iTBS. Correlation analysis between the Euclidean distance of treatment targets to the L-SFG and psychological scale scores revealed a significant negative association between the Euclidean distance and Generalized Anxiety Disorder-7 reduction rate.This exploratory study suggests that abnormal activity in the L-SFG and L-MFG underlies the variable efficacy of accelerated iTBS in adolescent depression. Our findings indicate that in an exploratory analysis, proximity to the L-SFG is correlated with treatment response, and L-MFG beta values showed slightly increased post-treatment. These preliminary results highlight these regions as potential neuroanatomical targets for future confirmatory research as biomarkers for iTBS mechanisms.